Trypanosomal diseases include some of the most pervasive and problematic illnesses facing man today. Of these, Chagas' disease, which is concentrated principally in Central and South America, is of particular concern, both for the number of individuals infected and for the lack of adequate chemotherapy to treat the disease (Brener, Z., Bull. WHO 60:463 (1982); Hammond et al., Trans. Royal Soc'y Trop. Med. Hyg. 78:91 (1984)). Although estimates of the extent of the disease vary, it is generally agreed that in excess of 10 million people are presently infected, representing in some reporting areas up to 43% of the total population. While the causative agent for Chagas' disease, Trypanosoma cruzi, is transmitted predominantly in rural areas by the reduviid bug, the disease is finding its way into urban areas through blood transfusion (Brener, A., Pharmacol. Ther. 7:71 (1979)). Chagas' disease is not presently a problem in North America, with only a few cases of indigenous Chagas' disease having been reported in the United States. However, T. cruzi is found in mammals and insects across the southern United States, as far north as Virginia (Downs, W. G., J. Parasit. 49:50 (1963)).
Although two agents which abolish parasitemia in the acute phase are presently available (Nifurtimox: (3-methyl-4-(5-nitrofurfurylidineamino) tetrahydro-4H-1,4-thiazine-1,1-dioxide) and Benznidazole: (N-benzyl-2-nitro-1-imidazoleacetamide)) (Keierszenbaum, F., Trop. Med Parasit., Mansfield ed., Marcel Dekker, New York (1984)), neither results in complete cure and both have serious side effects. Because of toxicity and the inability to completely abolish parasitemia with certainty, these drugs are not recommended as treatments for populations with chronic Chagas' disease. The unavailability of adequate chemotherapeutic agents for the treatment of Chagas' disease underlies the need for research of new antichagasic drugs.